Positron emission tomography (PET) is a powerful imaging tool to investigate biological function in living organisms. Small animals such as rats and transgenic mice serve as flexible surrogates for studying human disease and function. Consequently, small-animal PET has become a rapidly growing approach to problems in human health, from addiction to cancer to drug development. However, the best currently available PET technology (~2mm resolution) still has significant limitations in spatial resolution and sensitivity, particularly for the mouse. And currently proposed approaches to improve resolution face a number of technical obstacles which force trade-offs in performance. The goal of this project is to demonstrate the feasibility of a novel, high-performance, gamma-ray detection strategy for small-animal PET. It is essentially a miniaturized and modernized "Anger" (or "gamma") camera, with a principle similar to well-known detectors for single-photon emission computed tomography (SPECT), in which a continuous scintillator crystal is used and position is determined from light-sharing among groups of photodetectors. Critical improvements over the traditional design include a more appropriate scintillator for PET (LSO), a thinner crystal for higher resolution, and large-area avalanche photodiode (APD) technology as the photodetector which allows layering to improve sensitivity, among other benefits. Although many different implementations are possible, the target in this proposal is to develop a practical PET detector which, if used in a small-animal tomograph, achieves a uniform spatial resolution of 1 mm FWHM across most of the field-of-view, sensitivity larger than most small-animal detector designs, and a more cost-effective construction. The feasibility of the proposed detector design will be thoroughly characterized through the phases of prototype construction, performance evaluation, computer simulation development and validation, and finally optimization. The resulting optimized design is expected to provide an unparalleled combination of performance characteristics for small-animal PET imaging.